Prevalence of Micronutrient Deficiency in Patients with Morbid Obesity Before Bariatric Surgery

Background

Postoperative micronutrient deficiency is a known side effect of bariatric surgery. In this study, we examined the prevalence of micronutrient deficiency in patients with morbid obesity (MO) preoperatively.

Methods

A total of 1732 patients with MO wishing to undergo bariatric surgery (age: 40 ± 12 years, mean BMI: 44 ± 9 kg/m², means ± SD, 77.3% female) were analyzed in this cross-sectional examination. Iron state, vitamin B12, folic acid, 25hydroxy(OH)-vitamin D, PTH, vitamin A, and vitamin E levels were determined. Subsequently, patients underwent nutritional counseling and were substituted accordingly.

Results

A total of 63.2% (n = 1094) of the patients had a deficit in folic acid (< 5.3 ng/ml), 97.5% (n = 1689) in 25OHvitamin D (< 75 nmol/l), and 30.2% (n = 523) had a PTH elevation (> 56.9 pg/ml). A total of 5.1% (n = 88) of the patients presented with a deficit in vitamin B12 (< 188 pg/ml) and 6.2% (n = 107) in vitamin A (< 1.05 μmol/l). A total of 9.6% (n = 166) exhibited iron deficiency (ferritin < 15 μg/l). None of the patients had a deficit in vitamin E. There were no gender differences except for ferritin deficiency (women 11.8% vs. men 1.5%, p < 0.001). Patients in the highest BMI tertile had significantly more often a deficit in vitamin D (p = 0.033) and folic acid (p < 0.001). Patients in the lowest age tertile had significantly more often a deficit in folic acid (p < 0.001).

Conclusions

Our data show a high prevalence of micronutrient deficiency in patients with morbid obesity preoperatively and emphasize the importance of exact preoperative evaluation and adequate substitution as well as postoperative surveillance.

     

One-year glycemic control with a sulfonylurea plus pioglitazone versus a sulfonylurea plus metformin in patients with type 2 diabetes

OBJECTIVE: The goal was to assess the 1-year efficacy and safety of the addition of pioglitazone or metformin to existing sulfonylurea (SU) therapy in patients with inadequately controlled type 2 diabetes. RESEARCH DESIGN AND METHODS: In this multicenter, double-blind study, patients were randomized to receive either pioglitazone 15 mg (n = 319) or metformin 850 mg (n = 320) and up to 45 mg/day and 2,550 mg/day, respectively. The primary efficacy endpoint was HbA(1c) at week 52. Fasting plasma glucose, insulin, and lipid profiles were also measured. RESULTS: HbA(1c) was reduced by 1.20% in the SU plus pioglitazone group and 1.36% in the SU plus metformin group, and fasting plasma glucose was reduced by 2.2 and 2.3 mmol/l in the respective groups. Fasting insulin levels were also reduced (pioglitazone arm -1.3 micro IU/ml; metformin arm -0.8 micro IU/ml). There were no significant between-treatment differences in these three parameters. Pioglitazone addition to SU significantly reduced triglycerides (-16 vs. -9%; P = 0.008) and increased HDL cholesterol (14 vs. 8%; P < 0.001) compared with metformin addition. LDL cholesterol was increased 2% by the addition of pioglitazone and decreased 5% by the addition of metformin to SU (P < 0.001). Urinary albumin-to-creatinine ratio was reduced by 15% in the SU plus pioglitazone group and increased 2% in the SU plus metformin group (P = 0.017). Both combinations were well tolerated with no evidence of hepatic or cardiac toxicity in either group. CONCLUSIONS: Clinically equivalent improvements in glycemic control were observed for both combinations. Compared with metformin plus SU, addition of pioglitazone to SU resulted in a reduction of the urinary albumin-to-creatinine ratio, a small but significant rise in LDL cholesterol, and significantly greater improvements in triglyceride levels and HDL cholesterol levels. Metformin plus SU was associated with a significant reduction in LDL cholesterol. SU plus pioglitazone is an effective and well-tolerated combination regimen that may provide additional beneficial effects for patients with type 2 diabetes.     

Sodium-glucose linked transporter-2 inhibitor renal outcome modification in type 2 diabetes: Evidence from studies in patients with high or low renal risk

Data from three completed cardiovascular outcome trials (CVOTs), EMPA-REG OUTCOME, CANVAS Program and DECLARE-TIMI 58, add to the evidence supporting the potential renoprotective effects of sodium-glucose linked transporter-2 (SGLT2) inhibitors in patients with type 2 diabetes. Despite recommendations in recent guidelines, it is difficult to support a view that definitive evidence for renoprotection exists from these SGLT2 inhibitor CVOT results. To date, the only dedicated trial to report definitive data on the renal impact of SGLT2 inhibition is CREDENCE. Notably, the total number of patient-relevant renal endpoint events (dialysis, transplant or renal death) observed in CREDENCE was significantly higher than the total for all three CVOTs collectively (183 events/4401 patients vs. 69 events/34 322 patients, respectively), which shows the increased statistical power of CREDENCE for these renal endpoints. Treatment with canagliflozin was associated with a 30% relative risk reduction (RRR) in the primary composite endpoint of end-stage kidney disease, doubling of serum creatinine, or death from renal or cardiovascular causes and a 34% RRR for the renal-specific elements of this primary endpoint (P <0.001). Canagliflozin has therefore become the first US-approved SGLT2 inhibitor to include an indication for RRR, in addition to type 2 diabetes glycaemic control and cardiovascular risk reduction. While confirmatory of the exploratory data from CVOTs, CREDENCE provides the first robust data on the effects of canagliflozin on patient-relevant renal endpoints. Extrapolation to a conclusion of a SGLT2 inhibitor class effect cannot be made until additional renal trials with other SGLT2 inhibitors are reported.     

Four new cases of congenital secondary hypothyroidism due to a splice site mutation in the thyrotropin-beta gene: phenotypic variability and founder effect

Isolated TSH deficiency is a rare cause of congenital hypothyroidism. We here report four children from two consanguineous Turkish families with isolated TSH deficiency. Affected children who were screened at newborn age had an unremarkable TSH result and a low serum TSH level at diagnosis. Age at diagnosis and clinical phenotype were variable. All affected children carried an identical homozygous splice site mutation (IVS2 + 5 G--> A) in the TSHbeta gene. This mutation leads to skipping of exon 2 and a loss of the translational start codon without ability to produce a TSH-like protein. However, using specific monoclonal antibodies, we detected a very low concentration of authentic, heterodimeric TSH in serum, indicating the production of a small amount of correctly spliced TSH mRNA. By genotyping all family members with polymorphic markers at the TSHbeta locus, we show that the mutation arose on a common ancestral haplotype in three unrelated Turkish families indicating a founder mutation in the Turkish population. These results suggest that this TSHbeta mutation is among the more common TSHbeta gene mutations and stress the need for a biochemical and molecular genetic workup in children with symptoms suggestive of congenital hypothyroidism, even when the neonatal TSH screening is normal.     

YKL-40 is elevated in patients with peripheral arterial disease and diabetes or pre-diabetes

ObjectiveYKL-40 is secreted by macrophages in atherosclerotic lesions and involved in plaque rupture. YKL-40 is elevated in coronary artery disease, and predicts cardiovascular mortality. Experimental in vivo and in vitro data suggest a role of YKL-40 in tissue remodeling. A disease modulating potency of YKL-40 was not investigated in peripheral arterial disease (PAD).MethodsWe measured YKL-40 in 460 subjects: 316 PAD: 71 normal glucose metabolism (PAD-NGM), 90 pre-diabetes (PAD-PREDM) and 155 diabetes (PAD-DM); 20 diabetes with atherosclerosis but without PAD (AS-DM); 85 diabetes without macro-vascular complications (DM) and 39 healthy controls (CO).ResultsYKL-40 is higher in PAD vs. CO (median [25–75 percentile]: 103 [69–159] vs. 43 [30–80] ng/ml; p < 0.001). In addition, YKL-40 is elevated in DM (p < 0.001), PAD-NGM (p = 0.001), PAD-PREDM (p < 0.001), PAD-DM (p < 0.001) and AS-DM (p = 0.002) compared to CO. Among PAD, YKL-40 is increased in PAD-PREDM (p = 0.001) and PAD-DM (p = 0.01) vs. PAD-NGM. By multivariate regression YKL-40 is significantly associated with age (beta = 0.272), triglycerides (beta = 0.216), aspartate-amino-transferase (beta = 0.177) and c-reactive-protein (beta = 0.178). Underpinning its role YKL-40 was found to be associated with micro-/macroalbuminuria (p = 0.014/p = 008) – a strong remodeling inducer. In addition, YKL-40 was elevated in existence of mediasclerosis (p = 0.008), a remodeling process.ConclusionWe are first to show that YKL-40 is higher in subjects with peripheral arterial disease. YKL-40 was higher in PAD patients with pre-/diabetes. In addition, YKL-40 was associated with the “severity” of generalized atherosclerosis estimated by affected vascular beds. All our findings point towards a role of YKL-40 in the progression/prognosis of patients with PAD and concomitant diabetes.     

Goitrous congenital hypothyroidism and hearing impairment associated with mutations in the TPO and SLC26A4/PDS genes

CONTEXT: Pendred syndrome (PS) and thyroid peroxidase (TPO) deficiency are autosomal-recessive disorders that result in thyroid dyshormonogenesis. They share congenital hypothyroidism, goiter, and an iodide organification defect as common features. Whereas the hallmark of PS is sensorineural deafness, other forms of congenital hypothyroidism may also lead to hearing impairment. Therefore, a definite diagnosis may be difficult and require molecular genetic analyses. CASE REPORT: The propositus presented at birth with primary hypothyroidism and goiter. He also had congenital bilateral moderate hearing loss, and PS was suspected. METHODS: We sequenced the SLC26A4/PDS and TPO genes in the propositus and tested familial segregation of mutations in all available family members who were phenotypically normal. The functional consequences of the identified pendrin mutation (p.R776C) were studied in vitro. RESULTS: Sequencing of the SLC26A4/PDS gene revealed a single monoallelic missense mutation in the propositus (p.R776C). This mutation, which was inherited from his unaffected mother, has previously been identified in an individual with deafness and an enlarged vestibular aqueduct. Sequencing of the TPO gene revealed compound heterozygosity for a novel nonsense mutation (p.Q235X) and a known missense mutation (p.Y453D). The mutant pendrin (p.R776C) retained its ability to transport iodide in vitro. CONCLUSIONS: These results show that the propositus carries three sequence variants in two genes: a monoallelic SLC26A4/PDS sequence variant and compound heterozygous TPO mutations. Our study illustrates that if only a single heterozygous SLC26A4/PDS mutation is found in a patient with goiter and deafness, other genetic explanations should be considered.     

Cycles,phase synchronization,and entrainment in single-species phytoplankton populations

Complex dynamics, such as population cycles, can arise when the individual members of a population become synchronized. However, it is an open question how readily and through which mechanisms synchronization-driven cycles can occur in unstructured microbial populations. In experimental chemostats we studied large populations (>10⁹ cells) of unicellular phytoplankton that displayed regular, inducible and reproducible population oscillations. Measurements of cell size distributions revealed that progression through the mitotic cycle was synchronized with the population cycles. A mathematical model that accounts for both the cell cycle and population-level processes suggests that cycles occur because individual cells become synchronized by interacting with one another through their common nutrient pool. An external perturbation by direct manipulation of the nutrient availability resulted in phase resetting, unmasking intrinsic oscillations and producing a transient collective cycle as the individuals gradually drift apart. Our study indicates a strong connection between complex within-cell processes and population dynamics, where synchronized cell cycles of unicellular phytoplankton provide sufficient population structure to cause small-amplitude oscillations at the population level.